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https://www.readbyqxmd.com/read/28734961/radix-puerariae-modulates-glutamatergic-synaptic-architecture-and-potentiates-functional-synaptic-plasticity-in-primary-hippocampal-neurons
#1
Mohammad Maqueshudul Haque Bhuiyan, Md Nazmul Haque, Md Mohibbullah, Yung Kyu Kim, Il Soo Moon
ETHNOPHARMACOLOGICAL RELEVANCE: Neurologic disorders are frequently characterized by synaptic pathology, including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Therefore, to promote and/or protect synapses by the use of natural molecules capable of modulating neurodevelopmental events, such as, spinogenesis and synaptic plasticity, could offer a preventive and curative strategy for nervous disorders associated with synaptic pathology...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28734458/rett-like-severe-encephalopathy-caused-by-a-de%C3%A2-novo-grin2b-mutation-is-attenuated-by-d-serine-dietary-supplement
#2
David Soto, Mireia Olivella, Cristina Grau, Judith Armstrong, Clara Alcon, Xavier Gasull, Macarena Gómez de Salazar, Esther Gratacòs-Batlle, David Ramos-Vicente, Víctor Fernández-Dueñas, Francisco Ciruela, Àlex Bayés, Carlos Sindreu, Anna López-Sala, Àngels García-Cazorla, Xavier Altafaj
BACKGROUND: N-Methyl-D-aspartate receptors (NMDARs) play pivotal roles in synaptic development, plasticity, neural survival, and cognition. Despite recent reports describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatric diseases, little is known about their pathogenic mechanisms and potential therapeutic interventions. Here we report a case study of a 4-year-old Rett-like patient with severe encephalopathy carrying a missense de novo mutation in GRIN2B(p...
June 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28733356/steady-state-free-ca2-in-astrocytes-is-decreased-by-experience-and-impacts-arteriole-tone
#3
Eslam M F Mehina, Ciaran Murphy-Royal, Grant R Gordon
Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca2+ activity. However, whether resting astrocyte Ca2+ can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca2+ imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca2+ in the soma and endfeet. The drop in intracellular Ca2+ was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca2+ stores and nitric oxide...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28726541/characterization-of-postsynaptic-calcium-signals-in-the-pyramidal-neurons-of-anterior-cingulate-cortex
#4
Xu-Hui Li, Qian Song, Tao Chen, Min Zhuo
Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28725180/endothelial-nitric-oxide-synthase-is-present-in-dendritic-spines-of-neurons-in-primary-cultures
#5
Ariel Caviedes, Manuel Varas-Godoy, Carlos Lafourcade, Soledad Sandoval, Javiera Bravo-Alegria, Thilo Kaehne, Angela Massmann, Jorge P Figueroa, Francisco Nualart, Ursula Wyneken
Nitric oxide exerts important regulatory functions in various brain processes. Its synthesis in neurons has been most commonly ascribed to the neuronal nitric oxide synthase (nNOS) isoform. However, the endothelial isoform (eNOS), which is significantly associated with caveolae in different cell types, has been implicated in synaptic plasticity and is enriched in the dendrites of CA1 hippocampal neurons. Using high resolution microscopy and co-distribution analysis of eNOS with synaptic and raft proteins, we now show for the first time in primary cortical and hippocampal neuronal cultures, virtually devoid of endothelial cells, that eNOS is present in neurons and is localized in dendritic spines...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28719605/extracellular-phosphorylation-of-a-receptor-tyrosine-kinase-controls-synaptic-localization-of-nmda-receptors-and-regulates-pathological-pain
#6
Kenji Hanamura, Halley R Washburn, Sean I Sheffler-Collins, Nan L Xia, Nathan Henderson, Dipti V Tillu, Shayne Hassler, Daniel S Spellman, Guoan Zhang, Thomas A Neubert, Theodore J Price, Matthew B Dalva
Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28714867/enhanced-astrocytic-d-serine-underlies-synaptic-damage-after-traumatic-brain-injury
#7
Enmanuel J Perez, Stephen A Tapanes, Zachary B Loris, Darrick T Balu, Thomas J Sick, Joseph T Coyle, Daniel J Liebl
After traumatic brain injury (TBI), glial cells have both beneficial and deleterious roles in injury progression and recovery. However, few studies have examined the influence of reactive astrocytes in the tripartite synapse following TBI. Here, we have demonstrated that hippocampal synaptic damage caused by controlled cortical impact (CCI) injury in mice results in a switch from neuronal to astrocytic d-serine release. Under nonpathological conditions, d-serine functions as a neurotransmitter and coagonist for NMDA receptors and is involved in mediating synaptic plasticity...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713246/differential-contribution-of-ca-2-dependent-mechanisms-to-hyperexcitability-in-layer-v-neurons-of-the-medial-entorhinal-cortex
#8
Eric C Lin, Crescent L Combe, Sonia Gasparini
Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca(2+)-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28712640/resident-calmodulin-primes-nmda-receptors-for-ca-2-dependent-inactivation
#9
Gary J Iacobucci, Gabriela K Popescu
N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na(+) and Ca(2+) into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca(2+) transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. It also engages calmodulin (CaM) to reduce subsequent NMDA receptor activity in a process known as Ca(2+)-dependent inactivation (CDI). Here, we used whole-cell electrophysiology to measure CDI and computational modeling to dissect the sequence of events that underlies it...
July 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#10
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#11
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain IL-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28704576/psychosis-an-autoimmune-disease
#12
REVIEW
Adam Aj Al-Diwani, Thomas A Pollak, Sarosh R Irani, Belinda R Lennox
Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28703293/bmp-and-tgf%C3%AE-signaling-regulate-the-formation-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#13
Levi Todd, Isabella Palazzo, Natalie Squires, Ninoshka Mendonca, Andy J Fischer
Müller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGFβ/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Müller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28701532/basal-tree-complexity-shapes-functional-pathways-in-the-prefrontal-cortex
#14
Athanasia Papoutsi, George Kastellakis, Panayiota Poirazi
While the morphology of basal dendritic trees in cortical pyramidal neurons varies, the functional implications of this diversity are just starting to emerge. In layer 5 pyramidal neurons of the prefrontal cortex for example, increased basal tree complexity determines the recruitment of these neurons into functional circuits. Here, we use a modeling approach to investigate whether and how the morphology of the basal tree mediates the functional output of neurons. We implemented 57 basal tree morphologies of layer 5 prefrontal pyramidal neurons of the rat and identified morphological types which were characterized by different response features, forming distinct functional types...
July 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28699511/striatal-enriched-tyrosine-protein-phosphatase-step-in-the-mechanisms-of-depressive-disorders
#15
Elizabeth Kulikova, Alexander Kulikov
Striatal-enriched tyrosine protein phosphatase (STEP) is expressed mainly in the brain. Its dysregulation is associated with Alzheimer's and Huntington's diseases, schizophrenia, fragile X syndrome, drug abuse and stroke/ischemia. However, an association between STEP and depressive disorders is still obscure. The review discusses the theoretical foundations and experimental facts concerning possible relationship between STEP dysregulation and depression risk. STEP dephosphorylates and inactivates several key neuronal signaling proteins such as extracellular signal-regulating kinase 1 and 2 (ERK1/2), stress activated protein kinases p38, the Src family tyrosine kinases Fyn, Pyk2, NMDA and AMPA glutamate receptors...
July 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28688912/inhibition-of-the-kynurenine-pathway-protects-against-reactive-microglial-associated-reductions-in-the-complexity-of-primary-cortical-neurons
#16
Katherine O'Farrell, Eimear Fagan, Thomas J Connor, Andrew Harkin
Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP...
July 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28682239/physiological-and-pathophysiological-control-of-synaptic-glun2b-nmda-receptors-by-the-c-terminal-domain-of-amyloid-precursor-protein
#17
Paula A Pousinha, Xavier Mouska, Elisabeth F Raymond, Carole Gwizdek, Ghien Dhib, Gwenola Poupon-Silvestre, Laure-Emmanuelle Zaragosi, Camilla Giudici, Ingrid Bethus, Emilie Pacary, Michael Willem, Hélène Marie
The amyloid precursor protein (APP) harbors physiological roles at synapses and is central to Alzheimer's disease (AD) pathogenesis. Evidence suggests that APP intracellular domain (AICD) could regulate synapse function, but the underlying molecular mechanisms remain unknown. We addressed AICD actions at synapses, per se, combining in-vivo AICD expression, ex-vivo AICD delivery or APP knock-down by in utero electroporation of shRNAs with whole-cell electrophysiology. We report a critical physiological role of AICD in controlling GluN2B-containing NMDA receptors (NMDARs) at immature excitatory synapses, via a transcription-dependent mechanism...
July 6, 2017: ELife
https://www.readbyqxmd.com/read/28681915/17%C3%AE-estradiol-rescues-damages-following-traumatic-brain-injury-from-molecule-to-behavior-in-mice
#18
Huaihai Lu, Kun Ma, Liwei Jin, He Zhu, Ruiqi Cao
Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28680103/chemogenetic-silencing-of-gabaergic-dorsal-horn-interneurons-induces-morphine-resistant-spontaneous-nocifensive-behaviours
#19
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679049/role-of-mglu5-receptors-and-inhibitory-neurotransmission-in-m1-dependent-muscarinic-ltd-in-the-prefrontal-cortex-implications-in-schizophrenia
#20
Ayan Ghoshal, Sean P Moran, Jonathan W Dickerson, Max E Joffe, Brad A Grueter, Zixiu Xiang, Craig W Lindsley, Jerri M Rook, P Jeffrey Conn
Selective potentiation of the mGlu5 subtype of metabotropic glutamate (mGlu) receptor using positive allosteric modulators (PAMs) has robust cognition-enhancing effects in rodent models that are relevant for schizophrenia. Until recently, these effects were thought to be due to potentiation of mGlu5-induced modulation of NMDA receptor (NMDAR) currents and NMDAR-dependent synaptic plasticity. However, "biased" mGlu5 PAMs that do not potentiate mGlu5 effects on NMDAR currents show efficacy that is similar to that of prototypical mGlu5 PAMs, suggesting that NMDAR-independent mechanisms must be involved in these actions...
July 5, 2017: ACS Chemical Neuroscience
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